The broad, long-term objective is the development of analytic and statistical methods for the evaluation of interventions in infectious diseases. The specific aim is to develop analytic and statistical methods for evaluating efficacy of vaccines and effectiveness of vaccination programs against acute, directly transmitted infectious agents, such as acute, respiratory-related illnesses, given: heterogenous susceptibility of the target population, heterogenous action of the vaccine within the target population, different conditions of non-random mixing and transmission of infection, and vaccines that confer different types of protection, such as against infection or disease, or that reduce infectiousness. The experimental design and methods consist of: theoretical development and comparison of vaccine efficacy estimators and their standard errors based on: attack rates and transmission rates for randomly mixing populations, secondary attack rates for non-randomly mixing populations various methods of estimation, including maximum likelihood, log-linear models, least squares, martingales, and bootstrap, simulations using deterministic and stochastic models, analysis of data provided by the Immunization Branch of the CDC and the Task Force for Child Survival of the Carter Center.